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1、Yongge Wu School of Life Science School of Life Science National Engineering Laboratory for Aids VaccineNational Engineering Laboratory for Aids VaccineJilin UniversityJilin UniversityWhat is Biochemistry?Biochemistry is the study of the molecules and chemical reactions of life.It is the discipline
2、that uses the principles and language of chemistry to explain biology at the molecular level.Course OrganizationStatic part:Dynamic part:To introduce structure and function of biomolecules(proteins,nucleic acids,carbohydrates,lipids etc.)To introduce chemical actions,courses and reactions in living
3、systems,that is Metabolism.ProteinProteinEnzymeEnzymeCarbohydrateCarbohydrateLipidLipidNucleic AcidNucleic AcidVitaminVitaminHormoneHormoneMetabolism and energyMetabolism and energyCarbohydrate metabolismCarbohydrate metabolismLipid metabolismLipid metabolismProtein metabolismProtein metabolismNucle
4、ic acid metabolismNucleic acid metabolismGenetic information transmissionGenetic information transmissionContents of biochemistryThe TextbooksPrinciples of BiochemistryPrinciples of BiochemistryPrinciples of BiochemistryPrinciples of Biochemistry (3rd Edition)(3rd Edition)等主编，科学出版社等主编，科学出版社 2003.420
5、03.4生物化学（第三版）生物化学（第三版）生物化学（第三版）生物化学（第三版）王镜岩、朱圣庚等主编，高等教育出王镜岩、朱圣庚等主编，高等教育出版社版社 2002.92002.9Contents of Biochemistry(1)-This semesterChapter 1 Introduction to Biochemistry Chapter 2 WatersChapter 3 Amino Acids and Primary Structures of ProteinsChapter 4 Proteins:Three-Dimensional Structure and Function
6、 Chapter 5 Properties of EnzymesChapter 6 Mechanisms of EnzymesChapter 7 CarbohydratesChapter 8 Lipids and Membranes Chapter 9 Coenzymes and VitaminsChapter 1 Introduction to Biochemistry 1.1 Brief history of biochemistry1.2 What are the questions for biochemists to answer?1.3 Biochemistry and other
7、 disciplines.1.4 Application of biochemistry 1.5 Basic properties of living systems1.1 Brief history of BiochemistryPeriod 1 Period 1 Origin PhaseOrigin Phase the late century 18.the late century 18.Period 2Period 2Developing Developing PhasePhaseFrom From the the forepart forepart to to 40s of cent
8、ury 20.40s of century 20.Period 3Period 3Rapid Rapid Development Development PhasePhaseFrom From 1950s 1950s to to present.present.1780s Antoine Laurent Lavoisier(French):Combustion of a candle is similar to the“respiration”of animals,as both need O2.For the first time a physiological process was ex
9、plained with reference to a nonliving mechanism.Disaffirming“The Phlogiston Theory”Period 1Period 1 Origin Origin PhasePhase Modern Modern Biochemistry Biochemistry was was born born in in the the late late century century 18 18 as as the the development of Chemistry and Physiology.development of Ch
10、emistry and Physiology.vIn 1838,J.J.Berzelius(Sweden chemist)named the term“Protein”which was from Greek“proteios”,meaning“most important”.But he theorized“Vitalism theory”.vIn 1828，F.Whler(Germany Chemist，1800-1882）showed by synthesizing urea from ammonium cyanate that compounds found in living org
11、anisms could be made in the laboratory from inorganic substrances.Accordingly,he rejected the“Vitalism theory”V.Liebig(Germany Chemist，18031873）was one of founders of Biochemistry.Nutrient of food were divided into Carbohydrate,Lipid and Protein.Proteins from human and animal were same on structure
12、and properties.Protein was necessary for life.Carbohydrate can been transformd to Lipid.Carbon can been transformd to CO2 by oxygenation.Nitrogen can been transformed to urea.Brought the term“Metabolism”for the first time.Ferment was a soluble protein.Its function did not depend on the integrality o
13、f yeast cell.vLouis Pasteur(French microbiologist，1822-1895)His 3 major science achievements：1.Disaffirmed“Autogenetic theory”.Invent“pasteurism”。2.Every infectious disease was produced from a microorganism.Salvation French silk industry as found a invasion bacterial of silkworm.3.Invented Rabies va
14、ccine.But he thought mistakenly that ferment can only work in living yeast cell.1890s,E.Buchner(German):Yeast extract(no living cell)can ferment sugar to alcohol.Enzyme can function when removed from the living cell.Rejected “vitalism theory”.vIn 1878,W.Kuhne called them“Enzyme”for the first time.vI
15、n 1883,Anselme Payen(French chemist)discover Amylase.“-ase”was postfix of enzymes.He isolated Cellulose and named it.“-ose”was postfix of carbohydrates.vIn 1877,F.Hoppe-Seyler(Genman doctor)called the term“Physiological chemistry”for the first time.vOriginated“Journal of Physiological chemistry”vIso
16、lated Heme and obtained its crystal.In 1868,JFMiescher(Sweden doctor)isolated“nuclein”to be the founder of nucleic acid.In 1888,A.Kossel(German biochemist)proved“nuclein”was a complex of protein and nucleic acid.vIsolated 4 kinds of bases.vResearched the structure of nucleic acid.In 1911,P.A.T.Levin
17、e proved the structure of sugar from nucleic acid,and named it“Ribose”.vFound 2 kinds of diffenent nucleic acidRNA and DNA.vFounded nucleotide.vBut made mistakenly“Four nucleotide hypothesis”.Emil Fischer(German chemist)was one of founder of Biochemistry.vIn 1900s,he theoryzed“peptide bond theory”on
18、 protein structure.vInvented the method of peptide synthesis.vIn 1894,he theorized“Lock-Key theory”of Enzyme.In 1903,C.A.Neuberg(German)named the term“Biochemistry”.Established the“Glycolysis theory”.Period 2Developing Developing PhasePhaseFrom From the the forepart forepart to to 40s 40s of of cent
19、ury century 20,20,the the chemical chemical essence essence of of Enzyme Enzyme and and biomolecular biomolecular metabolism metabolism pathwayspathways were were discovered discovered with with the the technology technology improvement improvement of of purification purification as as chromatograpy
20、,chromatograpy,electrophoresis,electrophoresis,fluorescence fluorescence analysis,analysis,isotope,isotope,ultracentrifuge ultracentrifuge and and electronic electronic microscope.microscope.vIn 1926,J.B.Sumner(American chemist):crystalliztion of urease.He proved it is a protein.1912-1933,Biological
21、 oxidation was researched thoroughly.1930s,proved that Enzyme are protiens.In 1937,A.Krebs(English biochemist)discovered“Urea Cycle”and“Tricarboxylic Acid Cycle”(TCA Cycle,Krebs Cycle).In 1940s,glycolysis pathway and photo-synthesis were discovered.Discovery of Vitamin:In 1886,C.Eijkman(Netherland d
22、octor)In 1906 FrederickHopkins(English biochemist)In 1911,C.Funk(Poland chemist):Vatamin B1,Funk named it“Vitamine”,meaning“Vitalamine”.Later it was renamed as“Vitamin”.In 1912，Hopkins and Funk put forward“vitamin deficiency hypothesis”.Discovery of hormone:In 1902,EHStarling(English physiologist)an
23、d WMBayliss discovered Secretin(促胰液素促胰液素),In 1922,(Canadian physiologist)and purified Insulin.DNA carries genetic information:In 1928,FGriffith(English)-the experiment of bacteria transformation.In 1944,O.T.Avery(Canada)the experiment of bacteria transformation.In 1952,A.D.Herskey and M.Chase-T2 pha
24、ge.Bacteria transformation1.The colony of Wild-type Streptococcus pneumoniae is smooth(Type S).The colony of a mutant is rough(Type R).Their difference is on formation of capsule.capsulecolonytoxicityType SyessmoothyesType RnoroughnoGriffiths experimentConclusion:A substance from a dead toxic bacter
25、ium can transform into another living nontoxic bacterium.The process was called“Transformation”.The transformed substance was named“tranforming factor”.Averys experiment:Conclusion:The evidence presented supports the belief that a nucleic acid of the desoxyribose type is the fundamental unit of the
26、transforming principle of Pneumococcus Type III.(OSWALD T.AVERY,M.D.,COLIN M.MAcLEOD,M.D.,AND MACLYN McCARTY,*M.D.Studies On The Chemical Nature Of The Substance Inducing Transformation Of Pneumococcal Types Induction Of Transformation By A Desoxyribonucleic Acid Fraction Isolated From Pneumococcus
27、Type III.The Journal of Experimental Medicine.February 1,1944,Vol.79,No.2,pp.137-158)In 1946,G.Beadle(American biologist)and E.Tatum proved that a gene controls the synthesis of a enzyme.And they theorized“One gene one enzyme hypothesis”.Period Period 3 3 Rapid Rapid Development Development PhasePha
28、seFrom From 1950s 1950s to to present.present.The The composition,composition,sequence,sequence,structure structure and and function function of of biological biological macromolecular macromolecular such such as as protein,protein,enzyme enzyme and and nucleic nucleic acid acid were were researched
29、 researched profoundly.profoundly.Chemical Chemical synthesis synthesis technology technology was was been been greatly greatly developed.developed.Genetic Genetic engineeringengineering was established.was established.vIn 1950,Pauling put forward-Helix of protein secondary structure.vIn 1953,J.Wats
30、on&F.Crick established“DNA Double Helix Model”.It is the milestone of modern Molecular Biology.vIn 1958,F.Crick put forward“central dogma”.vIn 1966,Nirenberg&Khorana decoded genetic code.R.FranklinF.CrickJ.watsonM.Wilkins vIn 1953 and 1975,F.Sanger won two Nobel Prizes as the invention of methods of
31、 protein sequencing and nucleic acid sequencing respectively.vIn 1961,F.Jacob and J.Monod put forward“operon theory”.The inventor of DNA sequencing,double Nobel prize winner Fred Sanger vIn 1970,H.Temin and D.Baltimore found reverse transcriptase meantime.vIn 19721973,Paul Berg and Cohen etc.establi
32、shed DNA recombinant technology resulting in birth of“Genetic Engineering”.Basic procedure of gene cloning Basic procedure of gene cloning Target DNA fragmentRE digestionPlasmid RE digestionLigation Recombinant plasmidTarget DNA fragmentTransformation E.Coli without vector dieE.Coli with vector grow
33、Culture in the medium containing antibioticvIn 1975，E.Southern invented molecular hybridization to probe DNA”Southern Blot”.vIn 1982 and 1983，T.Cech and S.Altman discovered“ribozyme”respectively.vIn 1985，K.Mullis invented“Polymerase Chain Reaction(PCR)”.CechAltmanMullisHuman Genomic Project(HGP):In
34、1986,a Nobel prize winner R.Dulbecco published a paper in Science to first propose Human Genomic Project.In 1991,HGP began its research plan of 15 years.On June 26,2000,the working draft of Human gene sequence was published.vIn 1997，sheep Dolly-the first mammal to be cloned from an adult cell by I.W
35、ilmut.I.Wilmut-A usurper of Gods patent.Cloning OrganCloning OrganismGene therapy:In 1980,Martin Cline from University of California at Los Angeles tested his gene therapy ideas on patients with Thalassemia(地中海贫血症地中海贫血症),but failed to help his subjects.On Sep.14,1990,W.F.Anderson completed successfu
36、lly first gene therapy on A 4-year-old girl named Ashanthi DeSilva with adenosine deaminase(ADA)gene deficiency.It was a milestone of human gene therapy.On Sep.17,1999，A 18-year-old teenager Jesse Gelsinger with ornithine transcarboxylase deficiency(OTCD)received the gene therapy.Four days later,he
37、was dead.Achievement of China scientists on Biochemistry:In 30s，Xian Wu put forward“Denature theory of protein”.Cooperated with several teams first on chemically synthesis bovine insulin in 1965 and yeast alanine transfer RNA in 1983 respectively.1%sequencing DNA of HGP were completed by China.Gene
38、therapy medicine p53(Gendicine,今又生今又生)was marked first in the world.1.2 What are the questions for biochemists to answer?1.What are the biomolecules 2.(composition and structure)?2.How do biomolecules act and 3.interact?3.How are the biomolecules 4.synthesized(biosynthesis)?4.How is energy generated
39、 and consumed(energy metabolism,its source and fate)?5.How are the myriad of biochemical reactions regulated(the coordination problem,the network of control)?6.What is the carrier of genetic information and how is it expressed and transmitted(information pathway)?7.How do cells and organisms grow,di
40、fferentiate and reproduce?8.What is the molecular basis of evolution?9.What makes living organisms so diversified?(advantages,purposes and natural tendencies)10.How do we make use of life and knowledge about life for the benefits of human being(biotechnology,bioengineering)?ChemistryBiology BiochemistryPhysiologyGeneticsAuxologyEcology1.3 Biochemistry and other disciplinesCell BiologyMicrobiologyMedicinePharmacyChemical Biology1.Industry:2.Agriculture:3.Medicine and Health:4.1.4 Application of biochemistry